Isaac Kim
Assistant Professor

Roles of transforming growth factor- β and bone morphongenetic proteins in prostate cancer cells

The primary focus of our laboratory is the study of the tumor host interaction with the ultimate goal being the design of new and effective therapy for prostate cancer. The interaction between the host immune system and tumor is a multifaceted one with the generation of productive immunity requiring the cooperation of immune cells from multiple lineages. Further complicating the system, tumor cells themselves can produce immune suppressive factors.

A focus of current studies in our laboratory lies in understanding the role of tumor-derived bone morphogenetic proteins (BMPs) and TGF-beta on the local immune response, especially macrophages. Our findings suggest that BMPs and TGF-beta are major regulators of tumor-associated macrophages. Based on our findings, we are currently investigating various small molecule inhibitors as well as adoptive cell therapies to block the effect of tumor-derived BMPs and TGF-beta on tumor-associated macrophages in prostate cancer.

Selected Publications

Hong JH, Lee GT, Lee JH, Kwon SJ, Park SH, Kim SJ, Kim IY. (2008) Effect of bone morphogenetic protein-6 on macrophages. Immunology. Dec 23. [Epub ahead of print]

Lee GT, Hong JH, Mueller TJ, Watson JA, Kwak C, Sheen YY, Kim DK, Kim SJ, Kim IY. (2008) Effect of IN-1130, a small molecule inhibitor of transforming growth factor-beta type I receptor/activin receptor-like kinase-5, on prostate cancer cells. J Urol. 180(6):2660-7.

Jeon SS, Kim IY. (2008) Laparoscopic partial nephrectomy without hilar control. J Endourol. 22(9):1937-9; discussion 1941-2.

Lee GT, Hong JH, Kwak C, Woo J, Liu V, Lee C, Kim IY. (2007) Effect of dominant negative transforming growth factor-beta receptor type II on cytotoxic activity of RAW 264.7, a murine macrophage cell line. Cancer Res. 67(14):6717-24.

Shen SS, Smith CL, Hsieh JT, Yu J, Kim IY, Jian W, Sonpavde G, Ayala GE, Younes M, Lerner SP. (2006) Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer. 106(12):2610-6.

Abdelshehid, C, Ahlering, MT, Chou, D, Park, HK, Basillote, J, Lee, D, Kim, I, Eichel, L, Protsenko, D, Wong, B, McDougall, E, and Clayman, RV. (2005). Comparison of flexible ureteroscopes: deflection, irrigant flow and optical characteristics. Journal of Urology 173: 2017-2021.

Eichel, L, Kim, IY, Uribe, C, Khonsari, S, Basillote, J, Steward, E, Coad, J, Bischof, J, Rudie, E, Kluge, S, McDougall, EM and Clayman, RV. (2005) Comparison of radical nephrectomy, laparoscopic microwave thermotherapy, cryotherapy, and radiofrequency ablation for destruction of experimental VX-2 renal tumors in rabbits. Journal of Endourology 19: 1082-1087.

Kim, IY, Lee, DH, Lee, DK, Kim, WJ, Kim, MM, Morton, RA, Lerner, SP and Kim, SJ. (2004) Restoration of bone morphogenetic proteins receptor type II expression leads to a decreased rate of tumor growth in bladder transitional cell carcinoma cell line, TSU-Pr1. Cancer Research 64: 7355-7360.

Kim, IY, Lee, DH, Ahn, HJ, Kim, MM, Kim, SJ and Morton, RA. (2004) Loss of expression of bone morphogenetic protein receptor type II in human prostate cancer cells. Oncogene 23: 7651-7659.

Shariat, SF, Menesses-Diaz, A, Kim, IY, Muramoto, M, Wheeler, TM and Slawin, KM. (2004) Tissue expression of transforming growth factor-b1 and its receptors: correlation with pathologic features and biochemical progression in patients undergoing radical prostatectomy. Urology 63: 1191-1197.

Kim, IY, Lee, DH, Lee, DK, Kim, BC, Kim, HT, Leach, FS, Linehan, WM, Morton, RA and Kim, SJ. (2003) Decreased expression of bone morphogenetic protein receptor type II correlates with insensitivity to BMP-6 in human renal cell carcinoma cells. Clinical Cancer Research 9: 6046-6051.

Kim, IY, Kim, BC, Seong, DH, Lee, DK, Seo, JM, Kim, HT, Morton, RA and Kim, SK. (2002) Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis in androgen-independent human prostate cancer cell lines. Cancer Research 62: 5365-5369.

Kim, IY,Seong, DH, Kim, BC, Lee, DK, Remaley, AT, Leach, F, Morton, RA and Kim, SJ. (2002) Raloxifene, a selective estrogen receptor modulator, induces apoptosis in androgen-responsive human prostate cancer cell line, LNCaP, through an androgen-independent pathway. Cancer Research 62: 3649-3653.

Kim, HT,Kim, BC, Kim, IY, Mamura, M, Seong, DH, Jang, JJ and Kim, SJ. (2002) Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis through cleavage of BAD in human bladder cancer cells. Journal of Biological Chemistry 277: 32510-32515.

Lee, DK, Kim, BC, Kim, IY, Cho, EA, Satterwhite, DJ and Kim, SJ. (2002) The human papilloma virus E7 oncoprotein inhibits TGF-b signaling by blocking smad complex binding to its target sequence. Journal of Biological Chemistry 277: 38557-38564.

Shariat, SF, Kim, JH, Andrews, B, Kattan, MW, Wheeler, TM, Kim, IY, Lerner, SP and Slawin, KM. (2001) Preoperative plasma levels of transforming growth factor β1 strongly predict clinical outcome in patients with bladder carcinoma. Cancer 92: 2985-2992.

Kim, JH, Shariat, SF, Isaac Y. Kim, IY, Menesses-Diaz, A, Tokunaga, H, Wheeler, TMand Seth P. Lerner, SP. (2001) Predictive value of expression of transforming growth factor-beta(1) and its receptor in transitional cell carcinoma of the urinary bladder. Cancer 92: 1475-1483.

Young-Hyuck Im, Kim, HT, Kim, IY, Factor, VM, Hahm, KB, Anzano, M,Jang, JJ, Flanders, K, Haines, DC, Snorri S. Thorgeirsson, SS, Sizeland, A and Kim, SJ. (2001) Heterozygous mice for the transforming growth factor-b type II receptor gene have increased susceptibility to hepatocellular carcinogenesis. Cancer Research 61:6665-6668.

Shariat, SF, Shalev, M, Menesses-Diaz, A,Kim, IY, Kattan, MW, Wheeler, TM, and Slawin, KM. (2001) Preoperative plasma levels of transforming growth factor beta1 (TGF-b1) strongly predict progression in patients undergoing radial prostatectomy. Journal of Clinical Oncology 19: 2856-2864.

Kim, IY,Sadeghi, F, and Slawin, KM. (2001) Dyspareunia: an unusual presentation of leiomyoma of the bladder. Reviews in Urology 3: 152-154.